1. Field of the Invention
The present invention relates generally to the use of molecularly imprinted polymers comprising chelated lanthanides in methods and apparatus for detecting the presence of an analyte.
2. Description of the Related Art
Methods and apparatus for the efficient and accurate detection and quantification of analytes, including polyatomic anion analytes, are of particular interest for use in a wide range of applications. For example, such methods and apparatus are useful in the detection, monitoring, and management of environmental pollutants, including organophosphorus-based pesticides. Organophosphorus-based pesticides, including paraoxon, parathion, and diazinon are widely used in the agriculture industry. Because such materials exhibit a relatively high toxicity to many forms of plant and animal life, and also exhibit relatively high solubility in water, organophosphorus-based pesticides pose a clear threat to aquatic life and to our drinking water. Accordingly, it is imperative to be able to accurately monitor the levels of pesticides in industrial waste waters, agricultural runoffs, and other environments to determine compliance with federal and state regulations, and other safety guidelines.
The efficient and accurate detection of water-soluble anions is also of interest in a number of biomedical applications, including applications wherein it is desirable to detect anionic constituents in fluids associated with dialysis. For example, the detection of the build-up of phosphates in the blood is imperative to the treatment and/or control of renal failure and metabolic bone disease which is commonly associated therewith. Decreased renal function causes phosphates to build up in the blood. This increased serum phosphate combines with calcium, thereby lowering the serum calcium level. The fall in serum calcium levels, in turn, stimulates parathyroid hormone production, which dissolves bone in an effort to restore normal calcium levels. The result of lowered active vitamin D levels is impaired bone synthesis. The active form of vitamin D, normally made in the kidneys, assists in absorbing calcium and phosphorus, and promotes bone formation. Accordingly, the inevitable result of untreated chronic renal failure is bone disease. By monitoring the level of phosphates in the blood, renal failure patients may be better able to control the progression of metabolic bone disease.
Other applications for anion sensing include the detection of nitrates, phosphates, and the like in environmental and waste management applications. For example, nitrate run off from agriculture can cause problems for water quality, especially for children, resulting in the xe2x80x9cblue babyxe2x80x9d syndrome. Detecting dissolved nutrients, i.e. phosphate and nitrate, is a critical need for evaluating environmental pollution.
Applicants have come to appreciate, for many analyte-detecting applications, that the development of small, portable sensor devices which are relatively highly-selective and sensitive to a target analyte, and are capable of monitoring the analyte levels in real-time, is of particular interest. In certain embodiments, applicants have recognized it is further desirous for such portable sensor devices to operate using low-cost light and power sources.
Unfortunately, although a variety of techniques have been studied based on physical, chemical and biological sensing approaches, there are few conventional, low-cost and portable sensors with the capability to do real time monitoring/detecting of analytes. For example, methods for the unambiguous detection and quantitation of specific gaseous species usually involve separate sampling and analysis steps using complex and expensive devices such as gas chromatography with detection by either flame ionization or mass spectrometry. Much of the technology being used, such as gas chromatography-mass spectroscopy (GC-MS) and high performance liquid chromatography (HPLC), are large (not portable), expensive or require sophisticated, often extensive analysis procedures making them undesirable for real-time field analysis.
Furthermore, conventional optical sensors for the detection of aqueous analytes typically rely on small changes in the indices of refraction in response to the presence of an analyte. Commonly used, conventional optical sensors include planar waveguides, optical fibers, metallized prisms, and diffraction gratings. These and other conventional methods typically require extensive analysis procedures that can take up to 24 hours to perform. Although all these techniques have some degree of sensitivity, they lack specificity, rapid detection, real time analysis, easy operation, low cost, and portability.
Recognizing these and other disadvantages and drawbacks associated with conventional sensing methods and apparatus, applicants have developed the present invention.
The present invention overcomes the aforementioned disadvantages by providing optical sensors that are capable of detecting a variety of analytes, especially polyatomic anionic analytes, with a relatively high degree of selectivity and sensitivity, and also offer the advantages of real time analysis, easy operation, low cost, and portability. Applicants have discovered that molecularly imprinted polymers (MIPs) containing chelated lanthanides can be used to great advantage in optical sensors designed to detect any of a wide range of analytes. In particular, applicants have discovered that the lanthanide-containing MIPs of the present invention exhibit selective binding characteristics for a wide range of target analytes and thus allow for the detection of such target analytes with a relatively high degree of selectivity and sensitivity, and in less time and with fewer false positives than conventional optical sensors. In addition, applicants have discovered that the chelated lanthanides embedded within the present MIPs can be sensitized to absorb excitation energy provided by a low-cost light and power source, such as a light-emitting diode (LED), and to subsequently luminesce to allow for the detection of analytes. Accordingly, the sensors of the present invention tend to be low-cost, portable, yet highly effective, analyte sensors.
According to one aspect of the present invention, provided are sensor devices for detecting a target analyte. In certain preferred embodiments, the sensor devices of the present invention comprise a molecularly imprinted polymer containing a chelated lanthanide capable of binding the analyte to be detected, and which has operatively associated therewith: a light source for generating excitation energy for the chelated lanthanide of the molecularly imprinted polymer, wherein at least a portion of the excitation energy is absorbed molecularly imprinted polymer; and a detector for detecting luminescent energy generated by the chelated lanthanide upon excitation.
According to another aspect of the present invention, provided are methods of making a molecularly imprinted polymer comprising: mixing a lanthanide salt with one or more polymerizable/lanthanide-coordinating ligand compounds and a polyatomic anion target analyte under conditions effective to produce a chelated lanthanide-analyte complex; co-polymerizing the lanthanide-analyte complex with one or more cross-linking monomers and one or more matrix monomers to form a polymer structure; and removing the polyatomic anion from the polymer structure to form an MIP.